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Chen-Xu Ni, Yang Qi, Jin Zhang, Ying Liu, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Qiu-Ye Wu, Yan Wang, Jun-Ping Zhang
The eradication of cancer stem cells (CSCs) is significant for cancer therapy and prevention. In this study, we evaluated WM130, a novel derivative of matrine, for its effect on CSCs using human hepatocellular carcinoma (HCC) cell lines, their sphere cells, and sorted EpCAM+ cells. We revealed that WM130 could not only inhibit proliferation and colony formation of HCC cells, but also suppress the expression of some stemness-related genes and up-regulate some mature hepatocyte marker genes, indicating a promotion of differentiation from CSCs to hepatocytes...
October 22, 2016: Oncotarget
Daniel Wai-Hung Ho, Regina Cheuk-Lam Lo, Lo-Kong Chan, Irene Oi-Lin Ng
The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis...
October 2016: Liver Cancer
Samuel Kerk, Kelsey Finkel, Alexander T Pearson, Kristy Warner, Felipe Nor, Zhaocheng Zhang, Vivian P Wagner, Pablo A Vargas, Max S Wicha, Elaine Hurt, Robert E Hollingsworth, David A Tice, Jacques E Nor
PURPOSE: Loco-regional recurrence is a frequent treatment outcome for patients with advanced head and neck squamous cell carcinoma (HNSCC). Emerging evidence suggests that tumor recurrence is mediated by a small subpopulation of uniquely tumorigenic cells, i.e. cancer stem cells (CSC), that are resistant to conventional chemotherapy, endowed with self-renewal and multipotency. EXPERIMENTAL DESIGN: Here, we evaluated the efficacy of MEDI0641, a novel antibody-drug conjugate targeted to 5T4 and carrying a DNA-damaging "payload" (pyrrolobenzodiazepine) in preclinical models of HNSCC...
October 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Weizhong Sheng, Yusheng Chen, Yuda Gong, Tiangeng Dong, Bo Zhang, Weidong Gao
Anaplastic thyroid carcinoma (ATC) is aggressive and lethal with extrathyroidal invasion, distant metastasis, and resistance to conventional therapies. Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in ATC. MicroRNAs (miRNAs) have recently been found as an important class of cellular regulators of ATC carcinogenesis. Identification of CSC-related miRNAs and targets is therefore a priority for the development of new therapeutic paradigms. Patient-derived ATC cells were cultured in conditional media on poly-hema-treated dish...
October 25, 2016: Oncology Reports
Arvin Eskandari, Janine N Boodram, Paul B Cressey, Chunxin Lu, Peter M Bruno, Michael T Hemann, Kogularamanan Suntharalingam
We report the cancer stem cell (CSC) potency of a novel series of copper(ii)-phenanthroline complexes bearing nonsteriodial anti-inflammatory drugs: naproxen, tolfenamic acid, and indomethacin (2a-3c). Two of the complexes, 2a and 3c, kill breast CSC-enriched HMLER-shEcad cells (grown in both monolayer and three-dimensional cell cultures) to a significantly better extent than salinomycin, a well-established CSC toxin. The most potent complex in the series, 3c induces its cytotoxic effect by generating intracellular reactive oxygen species (ROS) and inhibiting cyclooxgenase-2 (COX-2) activity...
October 24, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Ying Liu, Yang Qi, Zhi-Hui Bai, Chen-Xu Ni, Qi-Hui Ren, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Lei Qiu, Jian-Zhong Li, Zhi-Gao He, Jun-Ping Zhang
AIM: Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, which has shown chemopreventive potential against various cancers. In this study, we evaluated the anticancer efficacy of a novel derivative of matrine, (6aS, 10S, 11aR, 11bR, 11cS)-10- methylamino-dodecahydro- 3a,7a-diaza-benzo (de) (MASM), against human hepatocellular carcinoma (HCC) cells and their corresponding sphere cells in vitro and in vivo. METHODS: Human HCC cell lines (Hep3B and Huh7) were treated with MASM...
October 24, 2016: Acta Pharmacologica Sinica
Kosuke Tanaka, Hirotaka Osada, Yuko Murakami-Tonami, Yoshitsugu Horio, Toyoaki Hida, Yoshitaka Sekido
Malignant mesothelioma (MM) frequently exhibits Hippo signaling pathway inactivation (HPI) mainly due to NF2 and/or LATS2 mutations, which leads to the activation of YAP transcriptional co-activator. Here, we show antitumor effects of statin on MM cells with HPI, through the interplay of the mevalonate and Hippo signaling pathways. Statin attenuated proliferation and migration of MM cells harboring NF2 mutation by accelerating YAP phosphorylation/inactivation. CD44 expression was decreased by statin, in parallel with YAP phosphorylation/inactivation...
October 20, 2016: Cancer Letters
Katsutoshi Mizuno, Erin E Dymek, Elizabeth F Smith
The complex waveforms characteristic of motile eukaryotic cilia and flagella are produced by the temporally and spatially regulated action of multiple dynein subforms generating sliding between subsets of axonemal microtubules. Multiple protein complexes have been identified that are associated with the doublet microtubules and that mediate regulatory signals between key axonemal structures, such as the radial spokes and central apparatus, and the dynein arm motors; these complexes include the N-DRC, MIA and CSC complexes...
October 22, 2016: Cytoskeleton
Margarida Ferreira-Teixeira, Daniela Paiva-Oliveira, Belmiro Parada, Vera Alves, Vitor Sousa, Obinna Chijioke, Christian Münz, Flávio Reis, Paulo Rodrigues-Santos, Célia Gomes
BACKGROUND: High-grade non-muscle invasive bladder cancer (NMIBC) has a high risk of recurrence and progression to muscle-invasive forms, which seems to be largely related to the presence of tumorigenic stem-like cell populations that are refractory to conventional therapies. Here, we evaluated the therapeutic potential of Natural Killer (NK) cell-based adoptive immunotherapy against chemoresistant bladder cancer stem-like cells (CSCs) in a pre-clinical relevant model, using NK cells from healthy donors and NMIBC patients...
October 21, 2016: BMC Medicine
Xinyi Liu, Dongfei Feng, Dianming Liu, Shuyuan Wang, Xuexin Yu, Enyu Dai, Jing Wang, Lihong Wang, Wei Jiang
BACKGROUND: Breast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate. METHODS: We identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length...
2016: PloS One
Gaia Palmini, Roberto Zonefrati, Carmelo Mavilia, Alessandra Aldinucci, Ettore Luzi, Francesca Marini, Alessandro Franchi, Rodolfo Capanna, Annalisa Tanini, Maria Luisa Brandi
The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients...
October 14, 2016: Journal of Visualized Experiments: JoVE
Sara S Franco, Karolina Szczesna, Maria S Iliou, Mohammed Al-Qahtani, Ali Mobasheri, Julianna Kobolák, András Dinnyés
Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current non-surgical treatments can cure cancer effectively. The reason could be due to the subpopulation called "cancer stem cells" (CSCs), being defined as those cells within a tumour that have properties of stem cells: self-renewal and the ability for differentiation into multiple cell types that occur in tumours...
September 30, 2016: BMC Cancer
Maggie Y Jiang, Tammy L Lee, Su-Shin Hao, Sepi Mahooti, Stephen M Baird, Daniel J Donoghue, Martin Haas
Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples...
October 18, 2016: Oncotarget
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Katherine Zukor, Hong Wang, Brett L Hurst, Venkatraman Siddharthan, Arnaud Van Wettere, Paul M Pilowsky, John D Morrey
Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography. The purpose of this study was to determine if the nature of the respiratory deficits in WNV-infected rodents is neurological and if deficits are due to a disorder of brainstem respiratory centers, cervical spinal cord (CSC) phrenic motor neuron (PMN) circuitry, or both...
October 19, 2016: Journal of Neurovirology
Qifang Long, Weipei Zhu, Jundong Zhou, Jinchang Wu, Weixian Lu, Cui Zheng, Dongmei Zhou, Ling Yu, Ru Yang
Ovarian cancer is one of the most lethal malignant gynecologic tumors with a high relapse rate worldwide. Cancer stem cells (CSC) have been identified in ovarian cancer and other malignant tumors as a small population of cells that are capable of self-renew and multi-differentiation. CD133 positive (CD133(+)) ovarian cancer stem cells have been reported to be more tumorigenic and more resistant to chemotherapeutic treatment. Thus, CD133 has emerged as one of the most promising therapeutic markers for ovarian cancer treatment...
October 18, 2016: Oncology Research
Kimberly F Starr, Eric A Porsch, Patrick C Seed, Christian Heiss, Radnaa Naran, L Scott Forsberg, Uri Amit, Pablo Yagupsky, Parastoo Azadi, Joseph W St Geme
Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269-492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), all encoding predicted glycosyltransferases...
October 2016: PLoS Pathogens
Li Lu, Menglin Wu, Longhao Sun, Weidong Li, Weihua Fu, Xuening Zhang, Tong Liu
BACKGROUND: In recent years, CD44 and CD133 have been identified as 2 common used cancer stem cell (CSC) markers in gastric cancer. However, the clinicopathological and prognostic value of these markers in gastric cancer remains controversial; moreover, there is lack of comparison of these 2 markers' roles in clinical applications. A systematic review and meta-analysis was conducted to elucidate these markers' clinicopathological features and association with prognosis in patients with gastric cancer...
October 2016: Medicine (Baltimore)
Theerawut Chanmee, Pawared Ontong, Tomomi Izumikawa, Miho Higashide, Nobutoshi Mochizuki, Chatchadawalai Chokchaitaweesuk, Manatsanan Khansai, Kazuki Nakajima, Ikuko Kakizaki, Prachya Kongtawelert, Naoyuki Taniguchi, Naoki Itano
Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. Like many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known on how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem-cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells...
October 6, 2016: Journal of Biological Chemistry
Yoo-Sun Kim, Eunju Kim, Yoon Jung Park, Yuri Kim
Neuroblastoma (NB) is childhood malignancy that retains characteristics of cancer stem cells (CSCs). Targeting the CSCs is one of the therapeutic strategies proposed to achieve complete remission of NB. β-carotene (BC), an active precursor of retinoids, is a well-known antioxidant reported to possess anti-CSCs effects. Here, we investigated the involvement of retinoic acid receptors (RARs) in the anti-CSCs effects of BC. Treatment with BC or retinoic acid (RA) upregulated RARβ mRNA expression in two NB cell lines...
October 14, 2016: Biochemical and Biophysical Research Communications
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